Depression‐like symptoms of withdrawal in a genetic mouse model of binge methamphetamine intake

Abstract

Binge methamphetamine (MA) users have higher MA consumption, relapse rates and depression-like symptoms during early periods of withdrawal, compared with non-binge users. The impact of varying durations of MA abstinence on depression-like symptoms and on subsequent MA intake was examined in mice genetically prone to binge-level MA consumption. Binge-level MA intake was induced using a multiple-bottle choice procedure in which mice were offered one water drinking tube and three tubes containing increasing concentrations of MA in water, or four water tubes (control group). In two studies, depression-like symptoms were measured using a tail-suspension test and a subsequent forced-swim test, after forced abstinence of 6 and 30 hours from a 28-day course of chronic MA intake. An additional study measured the same depression-like symptoms, as well as MA intake, after prolonged abstinence of 1 and 2 weeks. MA high drinking mice and one of their progenitor strains DBA/2J escalated their MA intake with increasing MA concentration; however, MA high drinking mice consumed almost twice as much MA as DBA/2J mice. Depression-like symptoms were significantly higher early after MA access was withdrawn, compared to levels in drug-naïve controls, with more robust effects of MA withdrawal observed in MA high drinking than DBA/2J mice. When depression-like symptoms were examined after 1 or 2 weeks of forced abstinence in MA high drinking mice, depression-like symptoms dissipated, and subsequent MA intake was high. The MA high drinking genetic mouse model has strong face validity for human binge MA use and behavioral sequelae associated with abstinence.